Plot
At a concert held by Green Day at Springfield Lake, they try to get an environmental message across to Springfield leading to their barge sinking in the highly polluted water, causing their death. Attending their funeral at the First Church of Springfield, Grampa is possessed and voices various ramblings leading to an eventual disaster. Marge takes these literally and tries to decipher them. Meanwhile, Homer does a poor job of fixing a sink hole in the backyard and when fixing the roof with Bart, Homer dares him to skateboard to Krusty Burger and back naked.

Bart is arrested and handcuffed to a pole naked, where eventually, Homer shows up with Bart's shirt, but no shorts. Inside, Flanders offers Bart some trousers and Homer sees Krusty make an advert where a pig is staring with a chefs hat. When Krusty orders the pig to be killed, Homer is upset and the pig makes a desperate attempt for freedom by running towards Homer, who adopts the pig, and naming him Spider-Pig. Also, in town, Lisa is trying to get a message about the environment out but doors are slammed in her face, while there, she meets a young Irish boy Colin. Lisa and Colin hold a town conference and manage to get Springfield to stop polluting the lake and clean it up. To avoid an environmental disaster.

When Marge asks Homer where Spider-Pig's waste is going, he shows her a silo in the back yard labelled "Pig Crap" and Marge asks Homer to dispose of it properly. As he takes it to a waste management facility, Homer gets a phone call from Lenny, who informs him of free donuts at Lardlad. Homer in his haste to be there, dumps the silo in the lake, thus polluting it, severely. When escaping from a predator a squirrel jumps in and is mutated to have sharp teeth and several dozen eyes. Flanders and Bart who are hiking spot the creature and it is captured by the Environmental Protection Agency.

Russ Cargill (Voiced by Albert Brooks) head of the EPA, and President Schwarzenegger have Springfield sealed off into a dome, with no escape. The cause of the dome's placement is found by the police and the entire town of Springfield is after the Simpsons raiding their home and setting it ablaze. As the Simpsons try to escape to the Flanders house, Spider-Pig, now renamed Harry Plopper, nudges them off and they fall to the ground and race to their car. It is picked up and sent towards five nooses. Marge, Bart, Lisa and Maggie make it safely to Bart's treehouse, while Homer is trapped in the noose with his arm inside it. To escape, Maggie shows the family how to get on the outside of the dome, the entire family follows Maggie, and as Homer escapes the House and car collapse in a earth slide.

The following day, The Simpsons flee and at the same time, Russ Cargill establishes a base around the dome and also gets President Schwarzenegger to approve destroying Springfield.

The Simpsons flee to a motel for the night, Homer reveals his plan to move the family to Alaska. At a nearby carnival, Homer wins a pick-up truck by winning in a Ball of Death game on a motorcycle. There family discover that they're wanted fugitives, and in the shop, Bart draws over the picture and a family of doppelgangers are arrested.

The Simpsons arrive in Alaska where they start to enjoy their new life. But when the news gets out from Tom Hanks (Voiced by himself) that the government is going to destroy Springfield, Marge wants to go home and save the town. But Homer refuses to help those who tried to kill him. Leaving the family to go to a local bar, he returns to find a video tape on the bed and Marge and the kids gone. The tape is from Marge stating that she is willing to leave her marriage and life with Homer to save the town.

Homer wanders around to look for his family, while on a train bound to Seattle, the EPA eavesdrops on Lisa and they are ambushed by Cargill, and arrested and sent back to Springfield.

Trying to find his family, Homer passes out unconscious in the cold. He is almost attacked where a native American woman, who Homer calls the "Boob Lady" and he realises that he should start to care about other people too and sets off to find his family back in Springfield. Back in Springfield Homer hears a sound which is Lisa's sax. Homer realises that his family has been captured and using a wrecking ball, he tries to save them but fails.

Inside the now practically destroyed town, Marge sees how bad things have gotten, and that the town has gone crazy and destroyed everything. Outside the dome, Homer knocks a guard out and finds some super glue in a nearby shack. Using his now sticky hands he ascends the side of the dome and into a hole created by Cargill to lower the bomb, which the town is trying to get rid off by using a diversion. Homer slides in and accidentally knocks the bomb off the rope and speeds up its count. Bart leaves to go to the church to be with Flanders. Who accepts him.

The entire town tries to figure out ways to disarm the bomb, but no luck, Homer finds a motorcycle and realises what he has to do. Homer grabs the bomb and Bart who then ascend from the side of the dome and throw the bomb out, it makes it out, just barely where it explodes and Homer and Bart are then thrown off into Springfield Gorge as the dome shatters into pieces. Cargill challenges Homer and Bart there wielding a shot gun. Maggie saves the two by dropping a boulder on Cargill. Homer is praised as a hero and the town starts rebuilding themselves, while Lisa and Colin walk away holding hands going out for Ice Cream.